Coated potassium chloride granules and tablets

ABSTRACT

This invention provides extended release potassium chloride granules consisting essentially of potassium chloride crystals having a mesh size of about 20–60 mesh that are coated only with ethylcellulose. The granules may be compressed into tablets that disintegrate rapidly in an aqueous environment to provide uniform dissolution of the potassium chloride. Tablets containing about 10 to about 20 milliequivalents potassium may be formulated in accordance with the invention. Processes to produce extended release granules without using surfactants, processing aids or other coating aids are also provided by this invention. A method is further provided whereby a patient&#39;s supplemental potassium requirements are met by administering an appropriate combination of dosage units chosen from available dosage units containing different quantities of potassium.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.10/076,892 filed on Feb. 14, 2002 now U.S. Pat. No. 6,780,437, entitled“Coated Potassium Chloride Granules and Tablets”; which is acontinuation-in-part of U.S. patent application Ser. No. 10/040,070,filed on Oct. 23, 2001 now abandoned, entitled “Coated PotassiumChloride Granules and Tablets.” The disclosure of each of the foregoingis incorporated herein by reference in its entirety.

BACKGROUND

This invention generally provides coated potassium chloride granulesthat may be used to make extended release potassium chloride tablets.Specifically, the present invention provides ethylcellulose-coatedcrystals of potassium chloride that may be orally administered to apatient requiring potassium supplementation. The coated potassiumchloride granules provide extended release of the potassium chloride inthe gastrointestinal tract that results in substantially less irritationto the gastric mucosa.

The administration of many diuretics, commonly used to treat patientshaving hypertension, increases the excretion of both sodium andpotassium. The acute administration of such diuretics to a patientnormally causes no problems. However, chronic administration ofdiuretics to some patients can result in the depletion of potassium fromthe patient, a condition known as hypokalemia. Potassium depletion maybe accompanied by a reduced tolerance to carbohydrates and a deficiencyin glycogen deposition. Further, vasopressin-resistant polyuria isanother complication. A deficit of potassium also appears to increasethe renal synthesis of prostaglandins, which in turn can decrease thepermeability to water of the distal nephron and produce a diabetesinsipidus-like syndrome.

In order to avoid these complications, supplemental potassiumadministration is typically needed. When potassium is taken along with anormal diet it is slowly absorbed from the intestinal tract. Followingpotassium distribution and uptake by the cells, the kidneys excrete anappropriate amount to maintain a proper balance. As a consequence of alarge volume of distribution and a rapid response of the kidney, theextracellular and intracellular concentrations of potassium are normallymaintained within relatively narrow limits.

When potassium is administrated as a drug, the factors that govern therate and extent of its distribution are of major importance. It is notpossible to increase the total cellular content of potassiumsignificantly above normal. However, it is very easy to raise theextracellular concentration excessively. It is the concentration ofpotassium in the extracellular fluid that determines life-threateningtoxicity.

It is well known that large doses of potassium chloride taken orally cancause gastrointestinal irritation, purging, weakness and circulatorydisturbances. Since potassium depletion can cause problems for thepatient, a controlled or extended release formulation of potassiumchloride that replenishes potassium in an acceptable manner withoutundesirable side effects is desired.

In an attempt to meet the need for suitable formulations that may beused as a potassium supplement, a number of different dosageformulations have been developed. U.S. Pat. No. 4,352,791 reports acomposition of potassium and a therapeutically acceptable salicylatesalt of salicylic acid. U.S. Pat. No. 4,340,582 reports an entericcoated tablet that may include potassium chloride. U.S. Pat. No.4,259,323 reports a potassium chloride emulsion. U.S. Pat. No. 4,259,315reports a controlled release potassium dosage from gelatin capsules thatcontain a mixture of ethylcellulose-encapsulated potassium chloride anda hydrophilic surfactant. Film-coated tablets containing potassiumchloride in a wax matrix (non-enteric coated) are marketed as a slowlyavailable potassium source. U.S. Pat. No. 4,235,870 reports a slowrelease pharmaceutical composition of a combination of higher aliphaticalcohols and hydrated hydroxyalkyl cellulose. U.S. Pat. No. 4,863,743reports a controlled release potassium chloride tablet made of potassiumchloride crystals coated with higher molecular weight (measuredviscosity greater than 40 cP in toluene/ethanol) ethylcellulose andhydroxypropylcellulose. U.S. Pat. No. 5,397,574 reports controlledrelease potassium chloride micropellets coated with lower molecularweight (measured viscosity less than 10 cP in toluene/ethanol)ethylcellulose and a plasticizer.

SUMMARY OF THE INVENTION

This invention provides a potassium chloride granule that contains bothcrystals of potassium chloride and a thermoplastic cellulose ether thatforms a coating on the crystals. No other agents, additives,surfactants, or coating and processing aids are used or included in thegranule. In one embodiment of the invention the potassium chloridecrystals have a size of about 20–60 mesh. In another embodiment thethermoplastic cellulose ether is ethylcellulose having a measuredviscosity of about 20 cP.

This invention also includes an extended release tablet made of aplurality of the ethylcellulose-coated potassium chloride granules. Thepotassium chloride granules that are in the tablet are essentially freeof surfactants or other processing additives and agents. The term“essentially free” indicates the absence of surfactants, additives,agents or coating and processing aids during the processing of thegranules.

The invention also includes dosage units having different potencies,including 10 milliequivalents (mEq) potassium per unit, 15 mEq potassiumper unit, and 20 mEq potassium per unit.

Further, the invention includes a process to produceethylcellulose-coated potassium chloride granules comprising the stepsof i) forming a fluidized bed of potassium chloride crystals at a dewpoint of about 10–20° C., ii) spraying the fluidized crystals with amixture of only ethylcellulose, alcohol and water sufficient to coat thecrystals, and iii) drying the coated crystals to remove the alcohol andwater to provide ethylcellulose-coated potassium chloride granules.

The invention also provides a process for producingethylcellulose-coated granules in which no additives are required duringthe spray-coating step for the control of static buildup in the fluidbed processor. The process comprises the steps of i) forming a fluidizedbed of potassium chloride crystals, ii) spraying the fluidized crystalswith a mixture consisting of ethylcellulose, alcohol, and sufficientwater to control the buildup of static charge to enable substantiallycomplete coating of the crystals, and iii) drying the coated crystals toremove the alcohol and water to provide ethylcellulose-coated potassiumchloride granules.

Also provided by the present invention is a method for customizing apatient's supplemental potassium dosage regimen. The method comprisesproviding dosage units (such as, e.g., tablets) having differentpotencies, and then administering to the patient a suitable combinationof dosage units to meet the patient's supplemental potassiumrequirements.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides an extended release potassium chloridetablet that includes ethylcellulose-coated potassium chloride crystals.No other surfactants or processing additives and agents are used in, orare part of, the coating.

In the practice of the present invention, one suitable method forcoating potassium chloride is by fluid-bed processing. Static buildup istypically controlled in ordinary fluid-bed processing methods by meansof a processing additive. One undesirable consequence of excessivestatic buildup is that particulate material may stick to the walls ofthe processing chamber, which can result in reduced yield or efficiency.The material sticking to the walls will be incompletely coated and maynot be included with the final product, leading to decreased yield.Material clinging to the chamber walls also complicates cleanup betweenprocessing runs. An additional consequence of the presence of excessivestatic is an increased risk of explosion. An explosion can be triggeredby static discharge in the fluid bed environment, due to the largeamounts of fine dust present and, in some cases, the presence of organicsolvent vapors.

Some common additives that are used to control static buildup includemagnesium stearate, titanium dioxide, and talc as well as commerciallyavailable products sold under the trade names STAT-LES by Walter G.Legge Company, Inc., Peekskill, N.Y., and LAROSTAT by PPG/MazerChemicals, Gurnee, Ill. Nonionic surfactants have also been used asadditives for static control. Suitable nonionic surfactants possess ahydrophilic-lipophilic balance (HLB) number in the range 4–15. Examplesof suitable nonionic surfactants include sorbitan monooleate (SPAN 80,HLB 4.3), polysorbate 60 (TWEEN 60, HLB 14.9) and polysorbate 80 (TWEEN80, HLB 15.0). The compositions and processes of the present inventiondo not require additives for static control.

Plasticizers are another class of processing additives that are commonlyused in the manufacturing process. A plasticizer can be used to changethe flexibility, tensile strength or adhesion properties of a polymericfilm. When used in a pharmaceutical coating, a plasticizer can be usedto improve or optimize the friability of a dosage unit or thedissolution profile of a delayed-release or extended-release dosageunit. Some common plasticizers that find use in pharmaceutical coatingapplications include dibutyl phthalate, diethyl phthalate, triethylcitrate, tributyl citrate, acetylated monoglyceride, acetyl tributylcitrate, dimethyl phthalate, benzyl benzoate, propylene glycol, butyland glycol esters of fatty acids, low-molecular-weight polyethyleneglycols, refined mineral oils, glycerin, oleic acid, organic acidesters, stearyl alcohol, castor oil, corn oil and camphor. Thecompositions and processes of the present invention do not utilizeplasticizers as additives for the thermoplastic polymer coating.

The active ingredient of the tablet provided by the present invention ispotassium chloride. Potassium chloride is administered to a patient insuch a manner in order to prevent or relieve potassium depletion and toavoid side effects. The potassium chloride tablets of the presentinvention may be co-administered with a diuretic.

Potassium chloride occurs in nature as the mineral sylvine or sylvite.Various industrial preparations of potassium chloride also existFurther, there are numerous pharmaceutical potassium chloridepreparations. Potassium chloride is a white crystal or crystallinepowder having the following physical description: d 1.98; mp 773° C.; 1gram dissolves in 2.8 ml water; 1.8 ml boiling water; 14 ml glycerol;about 250 ml ethyl alcohol; and is insoluble in ether and acetone.

In the present invention, potassium chloride crystals having a particlesize distribution ranging from about 20–60 mesh are subjected to coatingor encapsulation in ethylcellulose to produce coated potassium granules.The coated granules may subsequently be compressed into a tablet.

By providing a suitable coating weight of the ethylcellulose, athermoplastic cellulose ether polymer film may be formed on the crystalsthat remains intact in the stomach (and afterwards) but which ispermeable to gastric fluids. The gastric fluids dissolve and leach outthe potassium chloride contained in the coated crystals.

The thermoplastic polymer coating of ethylcellulose on the crystalsmakes up about 17% of the total weight of granules. Lesser amounts ofethylcellulose in the coating may lead to or cause the formation of barespots on the potassium chloride crystals during the compression step,leading to undesirably rapid release of the potassium chloride in thebody after oral administration. Greater amounts of ethylcellulose, asthe thermoplastic polymer coating, may cause the potassium chloride tobe released too slowly to be completely absorbed by the patient. In oneembodiment, potassium chloride is coated with ethylcellulose having asuitable molecular weight such as ethylcellulose designated as having aproduct viscosity of 20 and sold under the trademark ETHOCEL by DowChemical Company, Midland, Mich. The numerical designations forethylcellulose generally correspond to the viscosity of the product,with a greater numerical designation indicating a greater measuredviscosity and higher molecular weight. The 20 designation corresponds toa viscosity of about 18–22 cP as measured in a 5% by weight solution inan 80% toluene-20% ethanol solvent at 25° C. in an Ubbelohde viscometer.The ethoxyl content for ETHOCEL Standard 20 Premium cellulose ether isabout 48–49.5%.

In an embodiment of the invention, the individual crystals of potassiumchloride are coated with the appropriate materials to produce coatedgranules, which are mixed with acceptable compression aids anddisintegrants and then compressed into tablets. The tablets arecompressed in a manner so as to allow the tablets to disintegraterelatively quickly upon contact with an aqueous environment into theindividual coated granules, i.e., disintegration takes place in a shortperiod of time after oral administration.

The manufacturing process utilized in the present invention applies acontrolled and uniform coating, permitting uniform dissolution.Accordingly, the rapid disintegration and controlled dissolution of thetablets into individual granules and the controlled dissolution of thegranules permit the peristaltic motion of the gut to distribute thecoated granules over a wide surface area. As a result, concentratedquantities of potassium chloride do not come in contact with thegastrointestinal mucosa, thus reducing the undesired side effect ofgastric ulcers.

The importance of potassium supplement therapy has been wellestablished. Physicians need products for the prevention of hypokalemiaduring chronic diuretic therapy. Compliance is essential for patientsundergoing this type of therapy. Potassium chloride is normally providedin relatively large oral dosages in the range of 2 to 4 grams daily.Because of the large amount of the potassium chloride which is providedto the patient, gastrointestinal irritation is common. This irritationcan range from a slight discomfort to gastric ulcers. By includingpotassium chloride crystals in the granules in the manner indicatedabove and then compressing them in a conventional manner into tablets,the gastrointestinal irritation is alleviated or eliminated.

Dosages of supplementary potassium are measured in milliequivalents(mEq) of potassium per dosage unit. One mEq, which is equal to onemillimole, is provided by approximately 39 milligrams of potassium, orapproximately 75 milligrams of potassium chloride. The recommended dosefor most patients is 40 mEq per day in divided doses. In accordance withcurrently approved labeling a single dose of 20 mEq (or 2 doses of 10mEq) should be taken twice daily in order to obtain a daily dose of 40mEq. With the formulation provided by the present invention, suitabletablets will include a dose of 20 mEq so that the recommended effectiveamount of potassium per single dose would not be altered. The daily doseis achieved with one tablet twice daily thus facilitating compliance dueto less individual units per dose. Alternatively, other dosage unitshaving 10 mEq or 15 mEq are included in the present invention andprovide flexibility in establishing a regimen that meets a patient'sneeds.

In severe cases of hypokalemia, higher doses (60–80 mEq) of potassiummay be required to reduce the loss of potassium during high dosediuretic therapy. In such cases, the physician would have available asafe higher-strength tablet where, in his judgment, he is treating apatient with a compliance problem.

The tablets produced by the present invention disintegrate into numeroussub-units when placed in water or placed on an aqueous food. After beingdisintegrated into the sub-units or micro-pellets the potassium chlorideof the present invention can be more easily administered to children andgeriatric patients who often have difficulty in swallowing largetablets. The tablets may include conventional compression aids such asmicrocrystalline cellulose and disintegrants such as croscarmellosesodium. In addition, other additives may be beneficial. For example,magnesium stearate or stearic acid could be added as lubricating agent,if necessary, to the compositions and methods of the present invention.

The following formulation is suitable in the practice of the presentinvention for providing a dosage unit in tablet form having a potency of10 mEq: potassium chloride, 750 milligrams (75.3 wt.-%); ethylcellulose,154.4 milligrams (15.5 wt.-%); microcrystalline cellulose, 86.7milligrams (8.7 wt.-%); croscarmellose sodium, 5 milligrams (0.5 wt.-%).

The following formulation is suitable in the practice of the presentinvention for providing a dosage unit in the form of a tablet having apotency of 15 mEq: potassium chloride, 1125 milligrams (75.3 wt.-%);ethylcellulose, 231.6 milligrams (15.5 wt.-%); microcrystallinecellulose, 130 milligrams (8.7 wt.-%); croscarmellose sodium, 7.5milligrams (0.5 wt.-%).

The following formulation is suitable in the practice of the presentinvention for providing a dosage unit in the form of a tablet having apotency of 20 mEq: potassium chloride, 1500 milligrams (75.3 wt.-%);ethylcellulose, 308.8 milligrams (15.5 wt.-%); microcrystallinecellulose, 173.4 milligrams (8.7 wt.-%); croscarmellose sodium, 10milligrams (0.5 wt.-%).

The three exemplary formulations listed above for tablet-form dosageunits having the specified potency may be processed as follows: Thepotassium chloride is coated with a solution of ethylcellulose, waterand methyl alcohol using the fluidized bed process described below, toproduce coated potassium chloride granules. The coating solutionconsists of 87.6 wt.-% methyl alcohol (NF grade), 2.1 wt.-% water(purified, USP grade) and 10.3 wt.-% ethylcellulose (ETHOCEL Standard 20Premium). During the coating step, it is important to control the ratioof potassium chloride to ethylcellulose to achieve the desiredend-result formulations given above. Using the coating solutionindicated, to achieve the above-listed formulations the proper ratio(weight:weight) of coating solution to potassium chloride is 2.0:1.After coating, the potassium chloride granules are dried to remove allthe water and methyl alcohol. The granules are then blended withmicrocrystalline cellulose and croscarmellose to achieve the desiredend-result formulation, and the mixture is compressed into tablets usinga rotary tablet press. Using the formulations and quantities indicatedabove, the proper ratio (weight:weight) of coated potassium chloridegranules to microcrystalline cellulose (NF) is 10.4:1, and the properratio (weight:weight) of coated potassium chloride granules tocroscarmellose sodium is 181:1.

The invention further includes a process to produceethylcellulose-coated potassium chloride granules comprising the stepsof i) forming a fluidized bed of potassium chloride crystals at a dewpoint of about 10–20° C., ii) spraying the fluidized crystals with amixture of only ethylcellulose, alcohol and water sufficient to coat thecrystals, and iii) drying the coated crystals to remove the alcohol andwater to provide ethylcellulose-coated potassium chloride granules. Thealcohol solvent can be any of the low-boiling C₁–C₄ alcohols, such asethyl alcohol or isopropyl alcohol, and preferably methyl alcohol. Asuitable ethylcellulose/water/alcohol mixture for the practice of thisprocess is the 87.6 wt.-% methyl alcohol/2.1 wt.-% water/10.3 wt.-%ethylcellulose solution described above.

The invention also provides a process for producingethylcellulose-coated granules in which no additives are required duringthe spray-coating step for the control of static buildup in the fluidbed processor. The process comprises the steps of i) forming a fluidizedbed of potassium chloride crystals, ii) spraying the fluidized crystalswith a mixture consisting of ethylcellulose, alcohol, and sufficientwater to control the buildup of static charge to enable substantiallycomplete coating of the crystals, and iii) drying the coated crystals toremove the alcohol and water to provide ethylcellulose-coated potassiumchloride granules. A water content of approximately 0.5 to 2% by weighthas been found to be satisfactory for the control of static buildup inthe fluid bed processor. Water content up to about 4% by weight was alsofound to be effective, but the additional increment of water provided noadditional reduction in static buildup. The alcohol solvent can be anyof the low-boiling C₁–C₄ alcohols, such as ethyl alcohol or isopropylalcohol, and preferably methyl alcohol. A suitableethylcellulose/water/alcohol mixture for the practice of this process isthe 87.6 wt.-% methyl alcohol/2.1 wt.-% water/10.3 wt.-% ethylcellulosesolution described above.

A method is provided by the present invention, whereby a patient'ssupplemental potassium requirements may be met by utilizing a customizeddosage regimen. In the practice of this method, dosage units ofdifferent potencies are provided, and the patient's dosage regimen isdetermined by utilizing an appropriate combination of the dosage unitsto meet the patient's daily requirements of supplemental potassium. Thedosage regimen is then administered to the patient. The various dosageunits described herein are suitable for practice of this embodiment ofthe present invention.

By way of example, dosage units of 10 mEq, 15 mEq and 20 mEq potenciesmay be provided in the practice of this embodiment of the invention.Then, a patient requiring, for example, a daily supplemental dose of 30mEq potassium may be administered by any of the following regimens:twice-daily administration of 15 mEq dosage units; thrice-dailyadministration of 10 mEq dosage units; daily administration of one 10mEq dosage unit and one 20 mEq dosage unit.

Further, the method provides flexibility in meeting the needs of apatient whose daily requirement is, for example, 25 mEq, which is notreadily accomplished when dosage units containing 10 mEq and 20 mEq arethe only potencies available. A patient whose daily requirement is 25mEq potassium per day may be administered the following regimen: dailyadministration of one 15 mEq dosage unit and daily administration of one10 mEq dosage unit.

The present invention is further described in the following non-limitingexample.

COMPARATIVE EXAMPLE

Dosage proportional 10 mEq and 20 mEq tablets were compressed from ablend of materials listed in Table 1 which includesethylcellulose-coated potassium chloride granules. The Tablet A formulafor the coated potassium chloride granules included sorbitan monooleate(SORBITAN) added to the coating solution. The SORBITAN was added withsmall amounts of purified water to the coating solution during thecoating process, to reduce static buildup. The added purified water wasremoved during the coating process, but the nonvolatile SORBITAN wasretained in the polymeric coating. The Tablet B formula for the coatedpotassium chloride granules did not include SORBITAN.

TABLE 1 Tablet A Tablet B 10 mEq 20 mEq (wt. - 20 mEq 10 mEq 15 mEq(wt. - Ingredient %) (wt. - %) (wt. - %) (wt. - %) %) Sorbitan 0.4 0.4-0- -0- -0- Monooleate Potassium 75.0 75.0 75.3 75.3 75.3 ChlorideEthylcellulose 15.4 15.4 15.5 15.5 15.5 Microcrystalline 8.7 8.7 8.7 8.78.7 Cellulose Croscarmellose 0.5 0.5 0.5 0.5 0.5 Sodium Total mg/tablet1,000 2,000 996 1,494 1,992

A blend of the listed materials used to form a 400 kg lot was compressedinto both 10 mEq and 20 mEq tablets to provide Tablet A in two dosages.The dissolution profiles for the two tablets are listed in Table 2. Thedissolution specification for the 1, 2, 6 and 12 hour dissolution testpoints are: for one hour not less than 10% not more than 30%; for twohours not less than 20% not more than 60%; for six hours not less than50% not more than 90%; and for twelve hours not less than 85%.

TABLE 2 Tablet A 1 Hour 2 Hour 4 Hour 6 Hour 8 Hour 12 Hour 10 mEq with19% 34% 61% 79% 91% 100% SORBITAN 20 mEq with 18% 31% 56% 76% 91% 100%SORBITAN

A blend of materials listed in Table 1 was used to form 400 kg lot wascompressed into 10 mEq, 15 mEq and 20 mEq tablets to provide Tablet B inthree dosages. By increasing the amount of purified water added to thecoating solution by about 2% by weight, the SORBITAN was removed fromthe coating solution while still controlling the amount of static chargepresent in a Wurster Coater during the coating procedure. Thedissolution profiles for the three tablets are listed in Table 3.

TABLE 3 Tablet B 1 Hour 2 Hour 4 Hour 6 Hour 8 Hour 12 Hour 10 mEq 24%42% 67% 86% 98% 104% 15 mEq 23% 41% 68% 87% 97% 101% 20 mEq 24% 39% 64%87% 97% 104%

The revised Tablet B 10 mEq, 15 mEq and 20 mEq tablets meet the samedissolution specification used for the Tablet A 10 mEq and 20 mEqtablets. The data also indicates that the extended release properties ofboth sets of tablets are substantially the same, even though the TabletB set does not include SORBITAN.

Both Tablet A dosages and Tablet B dosages were made using knownprocesses. Briefly, a solution of ethylcellulose in methyl alcohol andwater (with and without SORBITAN, respectively) was sprayed ontopotassium chloride crystals in a 32-inch Wurster coater. The processparameters used for the coater are listed in Table 4.

TABLE 4 Bottom Plate Configuration G upbed plate, B downbed platePartition Height  25 mm Spray Nozzle Size 2.2 mm Spray Rate/Nozzle 600–1000 g/min Atomization Air Volume  50–60 cfm Product Temperature 45–60° C. Process Air Volume 2700–3700 cfm

After coating, the potassium chloride granules were then dried andblended with microcrystalline cellulose and croscarmellose sodium andcompressed into tablets using a rotary tablet press.

1. A method for customizing a patient's supplemental potassium dosagerequirement of about 25–80 mEq potassium comprising: i) providing atleast two individual pharmaceutical dosage units from the groupconsisting of a first individual dosage unit containing about 10 mEqpotassium, a second individual dosage unit containing about 15 mEqpotassium, and a third individual dosage unit containing about 20 mEqpotassium; and ii) administering a suitable combination of the 10 mEq,15 mEq, and/or 20 mEq individual dosage units that in single or multipleadministration meets the patient's supplemental potassium requirement,wherein each of the dosage units is an extended-release tabletcomprising a plurality of granules consisting of potassium chloridecrystals between about 20–60 mesh and having a continuous coatingconsisting of a single thermoplastic cellulose ether.
 2. A methodaccording to claim 1, wherein the administering is done occasionally. 3.A method according to claim 1, wherein the administering is done as adaily regimen.
 4. A method according to claim 1, wherein thethermoplastic cellulose ether is ethylcellulose.
 5. A method accordingto claim 1, wherein the single or multiple administration provides adosage in the range of about 25–45 mEq potassium.
 6. A method accordingto claim 1, wherein the patient's supplemental potassium dosagerequirement is about 30 mEq potassium or about 45 mEq potassium, andindividual pharmaceutical dosage units containing about 15 mEq potassiumare provided.
 7. A method for customizing a patient's supplementalpotassium dosage requirement of about 25–80 mEq potassium comprising: i)providing at least two individual pharmaceutical dosage units from thegroup consisting of a first individual dosage unit containing about 10mEq potassium, a second individual dosage unit containing about 15 mEqpotassium, and a third individual dosage unit containing about 20 mEqpotassium; and ii) administering a suitable combination of the 10 mEq,15 mEq, and/or 20 mEq individual dosage units that in single or multipleadministration meets the patient's supplemental potassium requirement,wherein each of the dosage units is an extended-release tabletcomprising a plurality of granules consisting of potassium chloridecrystals essentially free of surfactants or processing aids and agents,between about 20–60 mesh, and having a continuous coating consisting ofa single thermoplastic cellulose ether.
 8. A method according to claim7, wherein the administering is done occasionally.
 9. A method accordingto claim 7, wherein the administering is done as a daily regimen.
 10. Amethod according to claim 7, wherein the thermoplastic cellulose etheris ethylcellulose.
 11. A method according to claim 7, wherein the singleor multiple administration provides a dosage in the range of about 25–45mEq potassium.
 12. A method according to claim 7, wherein the patient'ssupplemental potassium dosage requirement is about 30 mEq potassium orabout 45 mEq potassium, and individual pharmaceutical dosage unitscontaining about 15 mEq potassium are provided.